With Reed and Sue Richards having a mutant kid, you would think there would be more mutant bad guys coming to their doorsteps to recruit the kid or possibly some anti-mutant groups causing trouble for the same reasons. It has happened a handful of times, but those were mostly one-time threats, I think there is room for a recurring villain there.

Batman vs Lex Luthor is a good one. Basically the two wealthiest, most intelligent and manipulative skill-monkeys in DC would make great opponents in a chess master sort of way.

Dr. Doom and Iron Man have had a few confrontations over the years, but you'd think they'd do so even more regularly. Tony is a man who was born into wealth and power, but learned humility when his life was saved and has since tried to use his wealth to better the world (when the writers weren't making him Iron Hitler). Doom was a man born into poverty who mastered science and sorcery to take over his country and has dedicated himself to taking over the world. Tony is basically the modern capitalist trying to improve the world, Doom is old school monarchy trying to build an empire.

Iron Fist versus the Mandarin seemed like something that could have happened as well. The Mandarin vs Iron Man was always good for the whole "ancient Eastern mysticism and martial arts" vs "modern capitalist science and technology", but you could see the Mandarin having just as much of a problem with Danny. Danny is another billionaire with a corporation, but he's also someone steeped in eastern mythology, which the Mandarin might hate as seeing some white infidel bastardizing his people's traditions. Could make for a cool fight and take a jab at the Mandarin's own racism. Though it might be weird that the Mandarin's big opponents both have 'Iron' in their name.

Given that the Rock of Eternity sits in the heart of existence and allows those bonded to it (Shazam, the Marvel Family, Black Adam) to travel through time, space and dimension, you wonder why more comics don't have Cap, Mary and Freddy policing the timeline and keeping extradimensional invaders out of the DC Universe. Stuff like Booster Gold's series would work great for them, and fighting invading mystical beings in the Cthulhu/Trigon vein would be right up their alley.

Has Kraven the Hunter ever fought Wolverine? You'd think a showdown between the two most 'hunter' focused archetypes would be a given.

There's a lot of street level types that you feel like Arcade should have fought more of, before stuff like Avengers Arena and that Avengers Academy crossover basically ruined the guy. Him being hired to kill Capt. America, Iron Fist & Luke Cage and the like could have made for some fun adventures. Throw Danny and Luke into some 70's style Kung Fu/Blacksploitation scenarios for a little extra adventure. The Heroes for Hire thing works as well since Arcade, Danny and Luke all are mercenaries to some extent.

Apocalypse or The Sphinx as Thor or Hercules opponents. Long-lived, mega-powerful baddies would make good opponents for those two. It'd be interesting to see what Apocalypse's whole "survival of the fittest" philosophy applies to gods.

The Red Skull, Baron Strucker and Baron Zemo vs the Black Panther. All three of them are master planners with large, powerful organizations who are also formidable personal threats. And they all do or have subscribed to Nazi philosophy at some point. Going after the most intelligent/wealthy/dangerous black man in Marvel seems like a natural conflict.

The Falcon vs the Vulture. Seriously, how many winged hero/villain fights have we seen?

Moon Knight vs Taskmaster. Two hooded master fighters taking each other on. Taskmaster is more skilled, forcing Moon Knight to either up his game or rely on craftiness and superior equipment. You could see Moony wanting to disrupt Tasky's supplying villains with thugs.

Moon Knight vs Dracula. Moon Knight started out fighting Werewolf by Night, a lot of his gear being lined with silver. Having Marc be an expert in the supernatural and a Blade-style monster hunter as well as a superhero could give him a unique niche. He'd have the right gear and give Dracula a modern 'skilled/gear' opponent as opposed to Blade or Dr. Strange.

Annihilus vs the Silver Surfer. Have these two ever fought? He seems like the right kind of cosmic threat for Norrin.

Iron Man vs AIM and HYDRA. There was a period during his Silver Centurion days where Tony fought AIM pretty regularly. That seems to have become less of a thing, but it makes sense. Put one of Marvel's greatest geniuses and arguably their greatest engineer against an evil group of mad scientists. Putting MODOK back in charge would even the odds a bit. Likewise, Tony's dad has some history with HYDRA, why not have Tony pick up where his dad left off, taking on Strucker and his latest advancements.

Iron Fist vs Gorgon and the Hand. Why not send one of Marvel's best martial artist against their big ninja cult and their superhuman warlord?

Captain Marvel vs Darkseid. Given how often Superman and Wonder Woman have gone up against Darkseid, and what Darkseid has tried to do to Cap's sister at one point, you'd think Cap would be more involved in New God matter. He doesn't even need a Boom Tube to get to Apocalypse or New Genesis, the Rock of Eternity can get him there.

Green Lantern vs Brainiac. You'd think the GL Corps would have gotten involved with the evil sentient robot going around abducting cities from planets across the universe.

Iron Man vs the Serpent Society. A supervillain group that runs itself like a corporation, with tons of snake-themed jobbers for Tony to fight? Sounds like a win.